Pharmacological effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine receptor system

Abstract

In mice, chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces an increase in the maximum number of [ 3H]spiperone binding sites in the striatum. The sensitivity of striatal protein phosphorylation to calcium plus calmodulin is also potentiated in MPTP-treated mice. These observations are associated with an enhancement of apomorphine-induced climbing behavior in the drug-treated animals. The results of this study suggest that in an animal model for Parkinson's disease, MPTP interrupts the dopamine (DA) transmission by chemically denervating the nigrostriatal neurons and through a compensatory mechanism, it increases the number of DA receptors as well as the sensitivity of protein phosphorylation to calcium plus calmodulin in mouse striatum. The latter two events may contribute to the development of DA receptor supersensitivity.